Antidiabetic Action of Mcy Protein: Studies on Gene Expression and Competitive Binding to Insulin Receptors

Mcy protein, isolated from the fruits of Momordica cymbalaria , was shown to have antihyperglycemic, antihyperlipidemic activities along with renal as well as hepatoprotective activities in streptozotocin-induced diabetic rats. Mcy protein was shown to have insulin-like structure and/or function and/or insulin secretagogue activity. Hence, the present study was conducted to elucidate the molecular mechanism whereby Mcy protein elicits its therapeutic role and also to know whether the Mcy protein has any structural and functional similarity with insulin. Results of our experiments revealed that the Mcy protein is insulin-like protein. Furthermore, we assessed the effect of treatment with Mcy protein on the glucose transport (levels of glucose transporter, GLUT-2) and on the levels of key regulators of glucose and lipid metabolisms like hepatic glucokinase (GK) and sterol regulatory element-binding protein-1c (SREBP-1c). Our findings demonstrated that Mcy protein elevated the expressions of GK, SREBP-1c, and GLUT-2 that were decreased in diabetic animals. Insulin-receptor binding studies using rat erythrocytes demonstrated that mean specific binding of insulin with insulin receptors was significantly increased in Mcy-treated diabetic rats when compared to diabetic control rats. Scatchard analyses of insulin binding studies yielded curvilinear plots, and the number of receptor sites per cell was found to be 180 ± 21.1 in Mcy-treated diabetic animals and found to be significantly superior to those of diabetic control animals. Kinetic analyses also revealed an increase in the average receptor affinity of erythrocytes of Mcy-treated rats compared to diabetic control rats suggesting acute alteration in the number and affinity of insulin receptors on the membranes of erythrocytes.